This application claims benefit under 35 USC xc2xa7371 of EP/01092 filed Feb. 19, 1999.
The invention relates to an analysis system, in particular for medical analysis work for carrying out clinical-chemical and immunological analyses.
Wet-chemical analysis systems, in which liquid reagents are provided in reagent containers which are held in suitable holders of a rotatable reagent rotor, are known. Furthermore, these known wet-chemical analysis systems have a sample rotor into which the samples contained in corresponding sample tubes are inserted. The reagent rotor is assigned a reagent pipettor, and the sample rotor is assigned a sample pipettor. A third rotor, a reaction rotor, is fitted with reaction cuvettes.
These known wet-chemical analysis systems operate as follows: the reagent pipettor is used to remove a predetermined amount of an analysis-specific reagent from the reagent containers contained in the reagent rotor and introduce this into a reaction cuvette, whereupon the sample pipettor removes a specified amount from a predetermined sample and introduces it into the reaction cuvette which has been filled with the reagent. The reaction cuvette, which in this way has been fed with a reagent and a sample, is moved from the reaction rotor to a measurement position, where, for example, a photometric measurement of the reaction solution is carried out, which is then evaluated on the basis of stored comparison values.
Wet-chemical analysis systems of this nature are suitable in particular for extensive series of tests or for a high incidence of analysis, as arises, for example, in clinical laboratories. Since the wet-chemical reagents contained in the open reagent vessels in the reagent plate have only a limited shelf life, a wet-chemical analysis system of this nature can only be operated if a certain minimum number of examinations are carried out in the system, since otherwise excessively frequent exchanging of reagents which have not been used but have expired is required, and this increases the operating costs.
As an alternative, a dry-chemical analysis system, in which reagents are applied to a carrier material in the solid state, is known. These reagent carriers are wetted with a predetermined amount of the sample, and the reagent carrier to which the sample has been applied is then examined in a detector device, for example by means of photometric measurement. However, these dry-chemical analysis systems have the drawback that the development costs for the reagent carriers are very high and that the samples generally have to be applied manually to the reagent carrier, so that these analysis systems are only suitable for single measurements or measurements with small numbers of samples or tests.
DE 33 18 573 A1 has disclosed an analysis appliance in which two concentrically rotatable rotors, i.e. an inner rotor for sample cuvettes and an outer rotor for measuring cuvettes, are provided, which rotors can be rotated independently of one another. Furthermore, in this appliance there is a pivotable working arm which, at its free end, is provided with a pipette. The pivot path of the pipette intersects the two rotors, so that in each case one measuring cuvette of the outer rotor and one sample cuvette of the inner rotor lie in the pivot path of the pipette. Furthermore, a measuring station, reagent bottles and a device for drying the pipette, as well as, if appropriate, a cleaning station for the pipette, are provided on the pivot path of the pipette, outside the outer rotor.
This known device operates as follows:
The arm with the pipetting device is pivoted over a sample cuvette located in the inner rotor, the pipette tip is immersed in the sample, and the sample is drawn into the pipette. The arm then pivots from the inner rotor to the outer rotor, above a measuring cuvette, and releases the sample into the measuring cuvette. Then, the measuring cuvette is taken hold of by a gripper situated on the arm, is lifted together with the arm, removed from the rotor and pivoted over the stationary measuring station, whereupon the measuring cuvette is lowered into the measuring station and released by the gripper. After this, the arm executes one or more further sequences of movements and, if appropriate after the pipette has first been cleaned, picks up one reagent or a plurality of reagents from the stationary reagent bottles, which are then injected into the measuring cuvette located in the measuring station. After the measurement has taken place, the measuring cuvette is returned to its position in the outer rotor by the arm.
A drawback of this known device is that the measuring cuvettes have to be transported out of and back to the rotor by the arm, making it necessary to provide the arm with a gripper, and consequently the arm structure becomes complex.
Furthermore, transporting the measuring cuvette from the outer rotor to the measuring station by means of the arm requires a certain time, during which the analysis appliance is not available for its actual task, i.e. for analysis.
DE 41 28 698 A1 has disclosed an analysis system in which sample vessels, reagent vessels and reaction vessels are arranged on a common rotor. This analysis system is equipped with a lifting pipettor which is arranged above the rotor edge and is able, by being lowered and raised, to pipette samples and reagent to and fro between different positions on the rotor, which rotates for this purpose. A photometric measuring station, which is able to carry out measurements on a fluid contained inside a reaction vessel in the rotor, is provided radially outside the rotor. The reagent vessels on the rotor of this known analysis system are formed by storage containers which are provided with dispensing openings, which the pipette tip of the pipetting arm can enter. Owing to the arrangement of the reagents on the rotor, and in particular within relatively large storage containers on the rotor, the number of reagents which can be used and/or the number of samples which can be analyzed is limited by the space available on the rotor, so that an analysis system of this nature can be used primarily for standardized, recurring tests which always use the same reagents.
EP 0,223,002 A2 has disclosed an automatic analysis system in which reagent carriers which are each provided with a plurality of holders are used. One of these holders serves as a measuring cuvette, one serves as a sample holder, and the other holders contain reagents. A plurality of reagent carriers are held next to one another in a magazine which can move in translation, it being possible to move the reagent-carrier holders of the magazine to in front of the entrance to a transfer station. The exit of the transfer station is directed towards spoke-like reagent-carrier holders of a rotary wheel. A system-reagent carrier which has been moved out of the magazine into the transfer station is processed in the transfer station, for which purpose pipetting and suction devices are connected to the transfer station. A sample which has been dealt with in the transfer station and is contained in an associated reagent carrier, after it has been dealt with in the transfer station, is transferred to the rotatable wheel, by which it is pivoted to in front of an optical analysis station, where the sample which is to be analyzed, which is located in the radially outer holder, is analyzed. The rotatable wheel of this known device therefore serves only as a means of transporting the reagent carriers.
The object of the present invention is to provide an analysis system in which both the appliance costs and the costs of the individual tests are low compared to the prior art and which has an extensive test menu and a simple work-flow concept, so that variable single-sample or multi-sample profiles can be carried out inexpensively.
This object is achieved by means of the analysis system, which comprises an analysis appliance and at least one system-reagent carrier, the analysis appliance having: at least one rotor which can be driven in controlled rotation, first holding devices for reagent vessels, second holding devices for sample vessels, a lifting/pivoting device which is provided with a pipetting device, can be driven in a controlled manner and can move towards and away from the rotor along a pivot path, a washing station for the pipetting device, a detector device and a control device for controlling the drive of the rotor and the drive of the lifting/pivoting device, and for controlling the operation of the pipetting device and the detector device, it being possible to place at least one sample vessel on the pivot path of the pipetting device, and the first holding devices being provided in the rotor, which forms a reaction rotor, and being designed to hold measuring cuvettes, the detector device being situated in the area of a corner position of the reaction rotor, so that the analysis takes place in a measuring cuvette which is located in the rotor, and the system-reagent carrier having at least one cuvette which is prefilled with a test-specific, preformulated, wet-chemical system reagent, as well as the measuring cuvette.
Preferably, the system-reagent carrier has a plurality of cuvettes which are arranged next to one another and are connected to one another, at least one of the cuvettes being prefilled with a test-specific, preformulated, wet-chemical system reagent.
Preferably, further cuvettes are arranged on two opposite sides of a central measuring cuvette, the opposite sides preferably being the radially inner and radially outer sides of the measuring cuvette which has been placed in a holding device, with reference to the radius of the reaction rotor. This design of a system-reagent carrier is advantageous in that the central measuring cuvette is used to hold the sample which is to be analyzed, to which the reagents, which are held in the side cuvettes, are added by pipetting. The sample which is contained in the measuring cuvette and has been mixed with the reagents can then be analyzed after the reaction rotor has been rotated to in front of the detector device.
The combination of an analysis appliance which is of relatively simple and inexpensive structure and the system.7 reagent carrier, which has one or more cuvettes which are filled individually, and in a test-specific manner, with system reagents, each cuvette being designed to carry out a single analysis operation, forms the basis of the inexpensive, flexible analysis system which allows the work to be carried out economically and inexpensively even for small to medium numbers of samples.
The cuvettes or the measuring cuvettes of each system-reagent carrier may in this case all be prefilled with the same reagent, resulting in a system-reagent carrier which is suitable for series testing of a multiplicity of different samples with regard to an analysis parameter. However, it is also possible to provide system-reagent carriers in which the cuvettes or measuring cuvettes are prefilled with different reagents, in order to carry out analyses on a single sample with regard to a multiplicity of analysis parameters.
Advantageously, the detector device has a photometric detector. In this embodiment, it is possible to carry out photometric measurements on the reaction solution, comprising sample and reagent, which is contained in the measuring cuvette to be tested.
Preferably, the second holding devices are formed by stationary holders which are arranged on a circular path which lies concentrically with respect to the pivot path of the lifting/pivoting device. This allows a very inexpensive design of the analysis appliance, in which only a single rotatable rotor, i.e. the reaction rotor, has to be provided, while the second holding devices are provided in a stationary position in the analysis appliance.
In an advantageous refinement, the second holding devices are provided on a second rotor which can be driven in controlled rotation, is of annular design and is arranged concentrically with respect to the reaction rotor. This configuration produces an analysis appliance with a higher throughput capacity, and allows the individual analyses to be carried out more flexibly.
Preferably, the second holding devices and the control device are designed in such a way that reagent containers can be inserted into the second holding devices. For certain cases, it is not only the mechanical insertion of the reagent containers into the second holding devices, but also the ability of the control unit to recognize a reagent container which has been inserted and to include this in the test process sequence, which make it possible to use specially prepared reagents which have been added to a reagent container or to use larger stores of a reagent, which is then provided in the reagent container, if the same reagent can be used, for example, for a plurality of tests.
Furthermore, it is particularly advantageous if reagent containers are provided, which are essentially compatible with the sample vessels, so that they can likewise be held by the second holding devices. This makes it possible to realize reagent containers with reagents which have been specially prepared for one analysis or various analyses (universal reagent) and which are not, or cannot be, produced at the level of system-reagent carriers. It is also possible for reagent containers of this nature to contain, for example, a dry-chemical reagent, should this be necessary for special analyses. The dry-chemical reagent should be dissolved manually or automatically prior to use. If a reagent container of this nature is inserted into one of the second holding devices together with sample vessels which are contained in other holding devices, it is preferable to provide an empty measuring cuvette in the first holding device for system-reagent carriers, for analysis purposes.
Preferably, a washing device for cleaning measuring cuvettes is provided. This washing device is advantageous in particular if the analysis uses empty measuring cuvettes into which both the sample and an externally supplied reagent are introduced, in which case the washed measuring cuvette can be used a number of times.
In another advantageous embodiment, the analysis appliance has a bound/free separation station. In this station, detectable substances which are not bound to the solid phase are separated off from the reagent, which is necessary when carrying out heterogeneous immunological tests, in which case a suitable specific solid phase is provided in the reagent, to which solid phase detectable substances are bound as a function of the analyte and in interaction with further reagent constituents.
In this case, it is particularly advantageous if the detector device has a photomultiplier for chemiluminescence measurement. This photomultiplier for chemiluminescence measurement may be provided in addition or as an alternative to a photometric detector, depending on the type of measurement or analyses for which the analysis system is to be designed.
Preferably, an evaluation unit, which evaluates the data recorded by the detector device using reference data which are stored in a memory device, is provided in the analysis system. However, the evaluation unit may also be formed by an external, commercially available computer, which is provided with suitable data and programs for evaluation and is connected to the analysis appliance of the analysis system via an interface.
If the analysis system is provided with an evaluation unit, a display device for displaying the results supplied by the evaluation device is preferably provided.
It is also possible to provide a printer device for printing out the results supplied by the evaluation device.
In a preferred configuration, the cuvettes are each closed off by means of a pierceable membrane. This ensures that the cuvettes are hermetically sealed until the analysis begins, with the result that the shelf life of the reagents contained in the cuvettes is increased noticeably, and therefore the storability of the system-reagent carriers is improved. Furthermore, it becomes possible to assess the condition of the reagent prior to measurement, making a subsequent diagnostic assessment even more certain.
The cuvettes or the system-reagent carrier may be provided with a machine-readable identification code for the respective reagent contained therein, and the analysis appliance may have a device for reading this identification code. This results in a higher level of automation when carrying out analyses, since each measuring cuvette which is to be filled with the sample, or the system-reagent carrier of this cuvette, is automatically detected, and the control device of the analysis appliance, as well as the evaluation device, are able to further process the data obtained from the reading device concerning the nature of the reagent contained in the corresponding measuring cuvette or in the corresponding system-reagent carrier and therefore concerning the test which is to be carried out with this reagent.
It is also particularly advantageous if the system-reagent carrier or the measuring cuvettes are in each case provided with a manufacturer identification coding or a manufacturer identification code, and if a recognition and decoding device is provided for this coding or code, the reading device advantageously being designed so that it can also read the manufacturer identification coding. In this way, it is possible to prevent system-reagent carriers or measuring cuvettes which are unsuitable for this analysis system from being used, since under certain circumstances this could lead to incorrect analysis results, and consequently the reliability of the analysis is increased further. Suitable coding may, for example, be effected mechanically (key-lock principle), electrically, electronically or optically, in which case the coding may also comprise an element which is protected in a different way, such as for example a trademark or a protected design element.
If the measuring cuvettes of a system-reagent carrier or individual system-reagent carriers are in each case connected to one another by means of desired breaking points, it is possible, when required, to separate individual or a plurality of measuring cuvettes from the system-reagent carrier or to separate system-reagent carriers from one another if, for example, only a few measuring cuvettes or system-reagent carriers are required for the tests which are to be performed.
The invention furthermore relates to an analysis appliance, in particular for an analysis system according to the invention, having at least one rotor which can be driven in controlled rotation, first holding devices for reagent vessels, second holding devices for sample vessels, a lifting/pivoting device which is provided with a pipetting device, can be driven in a controlled manner and can move towards and away from the rotor along a pivot path, a washing station for the pipetting device, a detector device and a control device for controlling the drive of the rotor and the drive of the lifting/pivoting device and for controlling the operation of the pipetting device and the detector device, it being possible to place at least one sample vessel on the pivot path of the pipetting device, and the rotor being designed to hold at least one measuring cuvette, in which analysis appliance the first holding devices are provided in the rotor, which forms a reaction rotor, and are designed to hold measuring cuvettes, and the detector device is situated in the area of a corner position of the reaction rotor, so that the analysis takes place in a measuring cuvette located in the rotor.
Advantageous refinements of the analysis appliance, which correspond to the appliance-specific advantageous refinements of the analysis system, are given.
The invention furthermore relates to a system-reagent carrier, in particular for an analysis system according to the invention, having at least one cuvette which is prefilled with a test-specific, preformulated, wet-chemical system reagent, the cuvette being provided with a machine-readable identification code for the reagent contained in the particular cuvette, and the analysis appliance having a device for reading the identification code, in which system-reagent carrier the cuvette or the system-reagent carrier is provided with a manufacturer identification coding which can be read and evaluated by a reading device of an associated analysis appliance.
An alternative system-reagent carrier is distinguished by the fact that a plurality of cuvettes, which are arranged next to one another and are connected to one another, are provided, at least one of the cuvettes being prefilled with a test-specific, preformulated, wet-chemical system reagent.
Preferably, a system-reagent carrier according to the invention is designed in such a way that a central cuvette, which is designed as a measuring cuvette, is provided, and that at least one further cuvette is provided in the system-reagent carrier at least on one side of the central cuvette, next to the top opening thereof, which further cuvette forms a holding chamber for a system reagent, the central cuvette and the further cuvette(s) forming a cuvette arrangement.
Advantageous refinements of the system-reagent carrier, which correspond to the refinements of the analysis system which are specific to the system-reagent carrier, are given.